Departments of Anesthesia, Pathology and Laboratory Medicine and Surgery, Medical University of South Carolina, Charleston, South Carolina

Discussion: The whole Blood platelet function test provided rapid results and the changes in collagen-activated platelet counts are consistent with the thrombocytopathy expected with CPB. ADP-induced platelet aggregation showed that essentially all platelets were active, a result not consistent with the well known platelet defect occurring during CPB (1,2). It is likely the 20 mM ADP used in the assay, which is 2-4 times the concentration used in conventional platelet aggregometry, is masking subtle platelet defects. Functional platelet studies during cardiac surgery may have a useful role guiding clinical and transfusion decisions.

Suboptimal Platelet Inhibition With Tirofiban in Patients Undergoing Coronary Intervention for Unstable AnginaSoffer D, O'Neill W, et al. William Beaumont Hospital, Royal Oak, Michigan, Lenox Hill Heart and Vascular Institute, New York, New York.
Abstract from American College of Cardiology, March 2002
Journal of Amer College of Cardio, March 6, 2002, Vol. 39, Issue 5, Suppl. A
Conclusion: "The current dose of tirofiban used in pts undergoing PCI for UA appears to be sub-optimal. Our findings may explain the mixed results of recent trials with tirofiban in such pts. Large-scale, prospective studies should evaluate whether tirofiban dose adjustment will have an impact on clinical outcome."

The Antiplatelet Activity of Clopidogrel is Inhibited by Atorvastatin but not by Pravastatin
Lau WC, Waskell LA, et al. Univ of Michigan, Ann Arbor, MI and Indiana Univ, South Bend, IN. Abstract from American Heart Association, November 2000.
Circulation (Suppl) 102:18, p II-429.
Conclusion: “These data suggest that atorvastatin is a competitive inhibitor of clopidogrel activation, where pravastatin is not. This suggests that clopidogrel activation may also utilize the CYP-450 3A4 system.”

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Clopidogrel Loading Prior to Coronary Stent Implantation: What is the Appropriate Dose?
Karatep M, Mani A, et al. Lenox Hill Heart and Vascular Institute, New York Abstract from Transcatheter Cardiovascular Therapeutics, November 2000.
Am J Cardiol 2000; 86(suppl 8A): 15i
Conclusion: “These data show that when clopidogrel is administered as a loading dose prior to coronary intervention, the 450mg dose should be accepted as the most effective loading dose. The clinical impact of these findings, if validated by randomized trials, should be considered prior to coronary intervention.”

What is the Appropriate Loading Dose of Clopidogrel Prior to Stent Implantation? Insights from a Platelet Inhibition Study
Soffer D, Taviloglu G, et al. Lenox Hill Heart and Vascular Institute, New York.
Abstract from American College of Cardiology, March 2000.
Journal Amer College of Cardio 2000; 35(Suppl A)
Conclusion: “These preliminary data suggest that when clopidogrel is administered as a loading dose prior to coronary intervention, a dose of 450mg appears to double the effect on platelet inhibition compared to 300mg in the time window of 3 to 9 hrs post bolus. The clinical impact of these findings, if validated by randomized trials, should be considered when planning the time of coronary intervention.”

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Validation of the Plateletworks Point of Care Platelet Function Analyzer
Sackett E, Nuttall G, et al. Mayo Clinic, Rochester, MN.
Abstract from Anesthesia and Analgesia 2000, S86.
Discussion: “In this ex-vivo addition trial of the Plateletworks - point of care platelet function analyzer, strong positive correlations were demonstrated when using all GPIIb/IIIa inhibitors. This leads to the conclusion that the device is an accurate measure of platelet function, and may be an effective device to guide drug administrations and may be useful in the operating room to assess platelet function.”

Evaluation of Abciximab Inhibition of Platelet Aggregation Using ICHOR Hematology Analyzer
Ogilby JD, Wolf NM, et al. Allegheny University of the Health Sciences, Philadelphia, PA and Indiana University, South Bend, IN.
Abstract from Int’l Society of Thrombosis and Hemostasis, 1999.
Conclusion: “The ICHOR can assess efficacy of these new agents while patients are in the catheterization laboratory undergoing interventional procedures. Further clinical studies are needed to document the usefulness of online analysis of platelet receptor blockade.”

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Testing Platelet Function in a Cardiopulmonary Bypass Patient Using a Near Patient Test System
Walker CT, Guyer KE, et al. Baptist Hospital, Pensacola, FL and Indiana University, South Bend, IN.
Thrombosis & Hemostasis 82(Suppl): 618 (Abst 1947), 1999.
Discussion: “This case report demonstrates that the ICHOR system has potential for the near patient evaluation of platelet function (aggregation in response to an agonist) which in this case avoided a second procedure which would have resulted in re-opening the chest, additional hemorrhage, risk of infection, hypothermia, and additional cost and length of stay. Such testing may also permit the differentiation between surgical bleeding and platelet dysfunction. This test may have clinical utility and application in the triaging of patients undergoing CPB procedures.”

Dose-Dependent Clopidogrel-Atorvastatin Drug-Drug Interaction Determined by Light Transmission Aggregometry
Wei C Lau, David GM Carville, Kirk E Guyer, Charlene J Neer, & Eric R Bates. University of Michigan, Ann Arbor, MI & Indiana University South Bend, South Bend, IN, USA.
Conclusions: A clopidogrel 450mg loading dose is as effective as 600mg in initially overcoming the clopidogrel-atorvastatin interaction seen with 300mg. However, the clopidogrel 75mg/d maintenance dose does not maintain platelet aggregation inhibition when co-administered with atorvastatin 40mg/d. Whether this remains a clinical phenomenon when additional subjects have been recruited to this group remains to be evaluated.